Review manuscript: Mechanisms of platelet activation by the pneumococcus and the role of platelets in community-acquired pneumonia

摘要

Highlights ? The pneumococcus promotes platelet activation. ? This is achieved by various mechanisms involving bacterial adhesins, pneumolysin and possibly H 2 O 2 . ? Pneumococcal and all-cause CAP are associated with alterations in blood platelet counts, particularly thrombocytopenia. ? Altered platelet counts in CAP are predictive of a poor outcome. ? Measurement of systemic biomarkers of platelet activation in CAP may have predictive potential. Summary There is increasing recognition of the involvement of platelets in orchestrating inflammatory responses, driving the activation of neutrophils, monocytes and vascular endothelium, which, if poorly controlled, may lead to microvascular dysfunction. Importantly, hyperreactivity of platelets has been implicated in the pathogenesis of myocardial injury and the associated particularly high prevalence of acute cardiovascular events in patients with severe community-acquired pneumonia (CAP), of which Streptococcus pneumoniae (pneumococcus) is the most commonly encountered aetiologic agent. In this context, it is noteworthy that a number of studies have documented various mechanisms by which the pneumococcus may directly promote platelet aggregation and activation. The major contributors to platelet activation include several different types of pneumococcal adhesin, the pore-forming toxin, pneumolysin, and possibly pathogen-derived hydrogen peroxide, which collectively represent a major focus of the current review. This is followed by an overview of the limited experimental studies together with a larger series of clinical studies mainly focused on all-cause CAP, which have provided evidence in support of associations between alterations in circulating platelet counts, most commonly thrombocytopenia, and a poor clinical outcome. The final section of the review covers, albeit briefly, systemic biomarkers of platelet activation which may have prognostic potential.